Upregulation of TMCO3 Promoting Tumor Progression and Contributing to the Poor Prognosis of Hepatocellular Carcinoma

查看全文 作　　者：Tianxing [1,2]Dai;Linsen [1,2]Ye;Mingbin [1,2]Deng;Guozhen [2,3]Lin;Rongqiang [2,4]Liu;Haoyuan [1,2]Yu;Wei [2]Liu;Yang [1]Yang;Guoying [4]Wang

机构地区：[1]Department of Hepatic Surgery and Liver Transplant Program,The Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong,China;[2]Guangdong Key Laboratory of Liver Disease Research,The Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong,China;[3]Department of Hepatic Surgery,The Third People’s Hospital of Shenzhen,Shenzhen,Guangdong,China;[4]Department of Hepatobiliary Surgery,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong,China

出　　处：《Journal of Clinical and Translational Hepatology》索引2022年第10卷第5期,共12页

基　　金：supported in part by grants from the Guangdong Natural Science Foundation(Nos.2015A030313038 and 2015A030312013);Guangdong Key Laboratory of Liver Disease Research(No.2017B030314027);National Natural Science Foundation of China(Nos.81770648 and 81972286). 摘　　要：Background and Aims:TMCO3,a member of the monovalent cation:proton antiporter-2 family,has been annotated as a Na^(+)/H^(+)antiporter,but its pathophysiological role is still unclear.We aimed to investigate the expression profile,prognostic significance,and oncogenic role of TMCO3 in hepatocellular carcinoma(HCC).Methods:Bioinformatic analyses were conducted using transcriptome data from public databases to determine the expression,prognosis,and functional enrichment of TMCO3 in HCC.TMCO3 expression was further validated in an independent HCC cohort from our institution.The oncogenic role of TMCO3 in HCC was evaluated using in vitro and in vivo experiments.Results:The upregulated expression of TMCO3 was identified and verified in multiple HCC cohorts,and worse overall survival and recurrence-free survival were observed in patients with high TMCO3 expression.The overexpression and knockdown of TMCO3 could affect the proliferation and metastasis of HCC cells,which might be associated with the p53-induced cell cycle regulation and epithelial-mesenchymal transition,respectively.Notably,significant correlations were found between dysregulated TMCO3 and various antitumor agents.Its role in sorafenib sensitivity was further identified by in vitro experiments and the potential mechanism might be related to the regulation of apoptosis.Positive correlations were also identified between upregulation of TMCO3 and the increased infiltration of various immune cells and the elevated expression of multiple immune checkpoint genes in HCC.Conclusions:Upregulated TMCO3 could act as an oncogenic mediator and promote sorafenib resistance in HCC,providing a potential therapeutic target for HCC treatment. 关键词：Hepatocellular carcinoma TMCO3 SORAFENIB Oncogene,prognosis

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Upregulation of TMCO3 Promoting Tumor Progression and Contributing to the Poor Prognosis of Hepatocellular Carcinoma

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